Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study

Abstract

Objective: To evaluate the effect of guselkumab on enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA).

Methods: This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0-3 on each digit; enthesitis was assessed using the Leeds Enthesitis Index (0-6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses.

Results: Of 149 randomised patients, 107 patients had enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of enthesitis and dactylitis. At week 56, mean improvements in enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in enthesitis and dactylitis versus non-responders (week 24).

Conclusions: At week 24, the guselkumab group had greater mean improvements in enthesitis and dactylitis and greater proportions of patients with resolution of enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in enthesitis and dactylitis.

Trial registration number: ClinicalTrials.gov: NCT02319759.URL: https://ichgcp.net/clinical-trials-registry/NCT02319759; Registered 18 December 2014.

Keywords: Ankylosing Spondylitis; Anti-TNF; Arthritis; Chemokines; Disease Activity; Lupus Nephritis; Psoriatic Arthritis; Rheumatoid Arthritis; Spondyloarthritis; Systemic Lupus Erythematosus; TNF-alpha; Treatment.

Conflict of interest statement

Competing interests: PJM has received research grants or served as a consultant or speaker for AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen Scientific Affairs, Novartis, Pfizer, Sun and UCB.DDG has received consulting fees and/or grant support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB.AD reports grants, personal fees and non-financial support from Janssen, during the conduct of the study; grants and medical writing support from AbbVie and Amgen; grants and personal fees from Eli Lilly; and grants, personal fees and medical writing support from Novartis, Pfizer and UCB.DGM has received research grants from AbbVie, Eli Lilly, Janssen, Novartis and Pfizer and has received honoraria from AbbVie, Celgene, Eli Lilly, Janssen, Pfizer and UCB.PN has received research funding for clinical trials and honoraria for advice and lectures on behalf of Abbvie, BMS, Celgene, MSD, Pfizer, Sanofi, Roche, Janssen, Gilead, UCB, Novartis, and Lilly.W-HB has received personal fees from Janssen, AbbVie, Almirall, Bristol-Myers-Squibb, Celgene, Eli Lilly, Janssen, Leo, Novartis and UCB, and grants from Pfizer.AG has received consulting and/or advisory board fees from AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Incyte, Janssen, Leo, Reddy Labs, Sun Pharmaceutical Industries, UCB, Valeant and Xbiotech, and grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB and Xbiotech.PSH has received research grants from AbbVie, Janssen and Novartis, and has received honoraria from AbbVie, Amgen, Celgene, Galapagos, Pfizer, and UCB.XLX, SX and ECH are employees of Janssen Research & Development, LLC, and own stock in Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary. CSK is an employee of Janssen Global Services, LLC, and owns stock in Johnson & Johnson, of which Janssen Global Services, LLC is a wholly owned subsidiary.

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Figures

Figure 1

Mean change from baseline in enthesitis score through week 24 (A) and week 56 (B) and mean change from baseline in dactylitis score through week 24 (C) and week 56 (D). Through week 24, missing data and data for patients who entered early escape were imputed using last observation carried forward (panels A and C); after week 24, no imputation was made for missing data, observed data were used and patients who early escaped or discontinued prior to week 24 were not included in the analysis (panels B and D). GUS, guselkumab; PBO, placebo.

Figure 2

The proportion of patients with resolution of enthesitis through week 24 (A) and week 56 (B) and the proportion of patients with resolution of dactylitis through week 24 (C) and week 56 (D). Through week 24, missing data and data for patients who entered early escape were imputed using last observation carried forward (panels A and C); after week 24, no imputation was made for missing data, observed data were used, and patients who early escaped or discontinued prior to week 24 were not included in the analysis (panels B and D). GUS, guselkumab; PBO, placebo.

Figure 3

Mean changes from baseline to week 24 in enthesitis score (A) and dactylitis score (B) among ACR20, ACR50, PASI 75, PASI 90, PASI 100 responders and non-responders in the guselkumab group. ACR 20/50, ≥20%/50% improvement in American College of Rheumatology criteria; PASI 75/90/100, ≥75%/90%/100% in Psoriasis Area and Severity Index score. ACR, American College of Rheumatology; PASI, Psoriasis Area and Severity Index.